β3-tripeptides act as sticky ends to self-assemble into a bioscaffold

Abstract

Peptides comprised entirely of β 3 -amino acids, commonly referred to as β-foldamers, have been shown to self-assemble into a range of materials. Previously, β-foldamers have been functionalised via various side chain chemistries to introduce function to these materials without perturbation of the self-assembly motif. Here, we show that insertion of both rigid and flexible molecules into the backbone structure of the β-foldamer did not disturb the self-assembly, provided that the molecule is positioned between two β 3 -tripeptides. These hybrid β 3 -peptide flanked molecules self-assembled into a range of structures. α-Arginlyglycylaspartic acid (RGD), a commonly used cell attachment motif derived from fibronectin in the extracellular matrix, was incorporated into the peptide sequence in order to form a biomimetic scaffold that would support neuronal cell growth. The RGD-containing sequence formed the desired mesh-like scaffold but did not encourage neuronal growth, possibly due to over-stimulation with RGD. Mixing the RGD peptide with a β-foldamer without the RGD sequence produced a well-defined scaffold that successfully encouraged the growth of neurons and enabled neuronal electrical functionality. These results indicate that β 3 -tripeptides can form distinct self-assembly units separated by a linker and can form fibrous assemblies. The linkers within the peptide sequence can be composed of a bioactive α-peptide and tuned to provide a biocompatible scaffold.

A two-dimensional metallosupramolecular framework design based on coordination crosslinking of helical oligoamide nanorods

“…Hybridizing natural a-peptides with unnatural b-oligoamides has been regularly used to enhance the diversity of folding conformations. [28][29][30] Hence, in this work a b 3 ,a hybrid oligoamide Ac-b 3 Fig. 1a) was designed to create metallosupramolecular superstructures (metallosupramolecular frameworks, or MSFs).…”

Transition of Nano-Architectures Through Self-Assembly of Lipidated β3-Tripeptide Foldamers

“…As a consequence, for the peptides used in this study, it can be proposed that the lipid side chains are all positioned on the same face of the 14-helix which provides the potential for the lipid chains are likely to align and pack in a layered arrangement. the orientation of the lipid chain on the surface of a fibril influences the lateral interactions This alignment then allows for fine control of the supramolecular structures formed by either limiting or promoting the amount of noncovalent interactions that drive lateral self-assembly and results in greater uniformity in fiber morphologies than previously described β 3 -peptides (Del Borgo et al, 2013Borgo et al, , 2018Seoudi et al, 2015Seoudi et al, , 2016Luder et al, 2016;Christofferson et al, 2018). The current results for the lipidated N-acetyl β 3 -tri-peptide foldamers therefore demonstrate a powerful design strategy to control fiber morphology through variation in the position of the alkyl chain.…”

“…The insertion of organic molecules between two β 3 -tripeptides did not prevent axial self-assembly, demonstrating how the tripeptides act as sticky ends due to the strength Abbreviations: AFM, atomic force microscopy; TEM, transmission electron microscopy; CD, circular dichroism. of the head-to-tail H-bonding motif (Del Borgo et al, 2018). The resulting fibrous scaffolds were also used as a biomaterial to successfully grow and maintain primary neuronal cultures.…”

Membrane active Janus-oligomers of β3-peptides

“…Consequently, in the last two decades peptidic foldamers, composed of non-natural amino acids, were intensively studied reaching structural diversity and widespread applicability similar to those of the natural biomolecules. [10][11][12][13][14][15][16][17][18][19] Their most commonly studied members are b-peptides, composed of bamino acids, where an additional methylene group is introduced between the peptide bonds. These compounds can adopt various secondary structures (helical, sheet-like conformations or hairpins) 15,17,[20][21][22][23][24][25][26][27] and even higher ordered aqueous assemblies such as helical bundles, 10,[28][29][30] protein-like assemblies [31][32][33][34][35] and nanobers.…”